Pharmacogenetics: The key to personalized therapeutic decisions

A popular cartoon encapsulates the hope and promise of personalized medicine, where drugs are prescribed based on an individual’s unique genetic make-up. The drawing features a woman standing at the pharmacy counter. Instead of handing the pharmacist a prescription for a medication, she hands him her genetic profile and says, “This is my genetic sequence. What medications are safe for me to take?” Although this may sound futuristic, clinicians are already making therapeutic decisions based on pharmacogenetic test results.

Pharmacogenetics merges the fields of pharmacology and genetics, allowing physicians to prescribe the best drug for each patient. Cyrine Eliana Haidar, PharmD, BCPS, BCOP, is the Clinical Pharmacogenetics Coordinator at St. Jude Children’s Research Hospital, where several medications are prescribed or dosed based on a patient’s genotype. Working with a multidisciplinary team, Haidar coordinates moving pharmacogenetic test results into a patient’s electronic medical record (EMR), allowing physicians and other members of the health care team to make medication decisions tailored to each patient. She is also responsible for developing education materials about pharmacogenetic tests and developing competencies and guidelines for implementing pharmacogenetics in clinical practice. “Pharmacists are the medication experts, and our understanding of medications and doses allows us to be perfectly placed to make decisions about medication use based on a patient’s pharmacogenetic status,” said Haidar, who has been with St. Jude for 9 years.

Clinical implementation

The pharmacy at St. Jude dispenses approximately 500,000 doses of medications used in the hospital, clinics, and procedure areas each year. An additional 80,000 prescriptions are filled for ambulatory outpatients. With so many critical and life-saving doses, it is important to get the right dose to the right patient every time.

In 2011, St. Jude launched PG4KDS, a protocol that uses pharmacogenetics as a tool to help improve medication safety and effectiveness. Each patient has a blood test to check for variations in 225 genes known to affect how the body handles drugs. Of the 225 genes, St. Jude currently uses data from two, CYP2D6 and TPMT, to make therapeutic decisions. “We can genotype hundreds of different genes on every patient, but we don’t really know yet what the variations in each gene mean,” said Haidar in an interview with Pharmacy Today. “As new data is published from groups doing basic science research in pharmacogenetics, my role is to say that we now have enough information in the published literature to have this genetic information available and in the EMR for patients at St. Jude.” The cost of the 225-gene panel is similar to the cost of two single-gene tests.

Currently, more than 1,000 patients have provided their consent to be enrolled on the PG4KDS protocol at St. Jude. These patients are battling cancer, HIV, and blood disorders.

Genes in action

TPMT is a gene that carries instructions for making an enzyme that breaks down a family of drugs known as thiopurines. Several thiopurines are important in the treatment of leukemia and lymphoma. Differences in TPMT mean that as many as 1 in 10 patients might benefit from a lower dose. “If we learn through genetic testing that a patient has a deficiency in that enzyme, then we know that up front, and everyone who treats that patient is alerted to the TPMT deficiency to make sure the patient does not receive the regular daily dose of mercaptopurine,” explained Haidar. “Instead, the patient will need to have their dose reduced by 90% and receive mercaptopurine three times per week.”

If a patient is prescribed a drug that should not be prescribed based on his or her genotype, a chain reaction of alerts ensues. E-mails are sent to Haidar, the patient’s physician, nursing staff, and any other clinical staff that works with that patient. In addition to the e-mails, an on-screen alert pops up in the patient’s EMR. Depending on the drug prescribed, the on-screen alert “says that your patient has a high priority genotype that has been linked to this medication,” Haidar told Today. “There is also specific wording about what you should do—either not give the medication or reduce the dose.”

As a double check, Haidar follows up with the medical staff to make sure the right dose was prescribed or an alternative medicine was given to the patient.

Patient and staff education

In addition to coordinating the transfer of genetic information into a patient’s EMR, Haidar is responsible for educating the clinical staff, patients, and their families about the new and growing field of personalized medicine. She created handouts for patients and their parents about genes, genetic tests, and the field of pharmacogenetics. Because patients and their families often ask nurses, physicians, or pharmacists about the implications of pharmacogenetic tests, Haidar provides education to the clinical staff. She is also involved with developing competencies and education material to teach clinical pharmacists how to enter a pharmacogenetic consult into the EMR. This consult tells the clinician how to interpret a genetic test result.

In collaboration with other institutions, Haidar is working on broader educational initiatives. The biggest challenge with implementing and moving pharmacogenetics into routine daily clinical practice is that there aren’t a lot of guidelines about what to do with the information, she noted. “I am collaborating with colleagues at St. Jude and other institutions to create guidelines for specific tests and genes to explain how you should dose medications based on certain genotypes,” said Haidar. Although there are some guidelines available, most are adult-specific, rather than pediatric-specific. “We are now looking at the guidelines for adults and researching how we can make them pediatric-specific,” she added.

As the field of pharmacogenetics continues to advance and become a more prominent tool for the treatment of disease, pharmacists are well positioned to become leaders in the field. Haidar believes that pharmacists should spearhead pharmacogenetic education and implementation efforts.

“The fact that my position exists shows that now is the time for pharmacogenetics and personalized medicine, and [pharmacists] have to take it from the current state to the next step by integrating it into clinical practice,” concluded Haidar.